烯丙基酚而非荧光素能增强成骨细胞中 PGD2 刺激的骨保护素和白细胞介素-6 的合成

IF 3
Tomoyuki Hioki , Gen Kuroyanagi , Rie Matsushima-Nishiwaki , Takuya Omura , Osamu Kozawa , Haruhiko Tokuda
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引用次数: 0

摘要

Gallein 是一种与荧光素有关的小分子,被认为是 Gβγ 亚基的抑制剂,可抑制 G 蛋白(Gs)信号传导。这种药剂是一种潜在的治疗策略,可改善器官功能障碍,尤其是与炎症有关的器官功能障碍,但其对骨代谢的影响尚未明确。前列腺素(PGs)在成骨细胞中发挥着重要的自分泌作用,d 型前列腺素(DP)受体是 G 蛋白偶联受体的成员之一,对 PGD2 具有特异性,可在成骨细胞中表达。我们以前曾报道过,前列腺素 D2(PGD2)可诱导骨重塑过程中必不可少的骨保护素(OPG)和白细胞介素-6(IL-6)的合成,而 p38 丝裂原活化蛋白激酶(MAPK)、c-Jun N 端激酶(JNK)和 p44/p42 MAPK 参与了 PGD2 在成骨细胞样 MC3T3-E1 细胞中的信号转导。因此,我们在本研究中探讨了 Gβɤ 亚基抑制剂 gallein 对 PGD2 诱导的 OPG 和 IL-6 合成的影响及其内在机制。用加勒林或荧光素(一种对 Gβɤ 亚基无活性的结构相关化合物)处理培养细胞,然后用 PGD2 刺激细胞。不是荧光素而是加来林扩大了 PGD2 刺激的 OPG 和 IL-6 的释放。加来宁增强了 PGD2 上调的 OPG 和 IL-6 的 mRNA 表达水平。在信号传导机制方面,加来林没有影响 PGD2 诱导的 p38 MAPK、JNK 或 p42 MAPK 的磷酸化。总之,加来林通过抑制成骨细胞中Gβγ亚基的特异性作用来上调PGD2刺激的OPG和IL-6的合成,但这种作用并不是在p38 MAPK、JNK或p44/p42 MAPK激活的上游发挥的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gallein but not fluorescein enhances the PGD2-stimulated synthesis of osteoprotegerin and interleukin-6 in osteoblasts

Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gβγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and d-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD2, is expressed on osteoblasts. We previously reported that prostaglandin D2 (PGD2) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD2 in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gβɤ subunits, on the syntheses of OPG and IL-6 induced by PGD2 in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gβɤ subunits, and subsequently stimulated with PGD2. Not fluorescein but gallein amplified the PGD2-stimulated releases of OPG and IL-6. Gallein enhanced the PGD2-upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD2-induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD2-stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gβγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation.

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来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
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64 days
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